Interferon Responses in Eczema Herpeticum

NCT01429311 | Completed

• 2 other identifiers: DAIT ADRN-01NIAID Funding Mechanism
• Study Type: observational
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Atopic dermatitis (AD) is a chronic skin disorder characterized by recurrent viral skin infections. A small subset of patients with AD suffer from disseminated viral infections, e.g., eczema herpeticum (ADEH+), after herpes simplex infection (HSV) or eczema vaccinatum (EV) after smallpox vaccination. Interferon gamma (IFNγ) plays a critical role in the innate and acquired immune responses by activating macrophages, enhancing natural killer cell activation, and promoting T cell differentiation, as well as regulating B cell isotype switching to immunoglobulin (Ig) G2a. Recent studies have demonstrated that IFNγ generation was significantly decreased after stimulation with HSV ex vivo. The purpose of this study is to determine if deficient IFNγ induction leads to susceptibility to HSV infection in ADEH+ patients.

Conditions

Atopic Dermatitis; Eczema Herpeticum; Herpes Simplex Infections; Eczema Vaccinatum

Keywords

Atopic Dermatitis; Eczema herpeticum; Interferon gamma; IFNγ

Outcome Measures

Primary Outcomes (1)

• Expression of IFNγ and Interleukin-12 (IL-12), in response to stimulation with Herpes Simplex Virus 1 (HSV-1), Vaccinia Virus (VV), and Pattern Recognition Receptors (PRR) agonists

  Protein and messenger ribonucleic acid (mRNA) levels of IFNγ, and the IFN-γ promoting cytokine, IL-12, produced by Cluster of Differentiation 14 (CD14+) monocytes in response to stimulation with HSV-1, VV, and various PRR agonists

  Day 1

Secondary Outcomes (10)

• Cell surface expression of Major Histocompatibility complex (MHC) class I and class II and co-stimulatory molecules on CD14+ cells in response to IFNγ and Interferon-alpha (IFNα) stimulation

  Day 1

• Production of IL-18 and IFNα protein and mRNA by CD14+ cells following stimulation with HSV-1, VV, or PRR agonists

  Day 1

• Production of IFNγ protein by Cluster of Differentiation 8 (CD8+) T cells in response to stimulation with recombinant human cytokines including but not limited to IL-12, IL-18, and IFNα

  Day 1

• Protein expression of IFNγ receptor and IFNα/β receptor on CD14+ cells

  Day 1

• Immunodominant HSV-1 peptide repertoires

  Day 1

Study Arms (3)

ADEH+

Subjects classified as Atopic Dermatitis (AD) and history of previous Eczema Herpeticum (EH) as defined by the ADRN Standard Diagnostic Criteria

ADEH-

Subjects classified as AD without a history of EH as defined by the ADRN Standard Diagnostic Criteria

Non-atopic Controls

Subjects classified as "Non-Atopic controls" as defined by the ADRN Standard Diagnostic Criteria

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

40 ADEH+, 40 ADEH-, and 40 non-atopic controls ages 6 to 65 years. Initially, 20 ADEH- and 20 non-atopic control participants will be gender- and age-matched (plus or minus 10 years) to 20 ADEH+ participants. Afterwards, additional participants will be enrolled such that the gender ratio and the age distribution of the ADEH+ participants will be similar to that of the ADEH- and non-atopic control participants

You may qualify if:

• Participants who meet all of the following criteria are eligible for enrollment:
• have a history of AD with or without a history of Eczema Herpeticum (EH) as diagnosed using the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria OR
• are non-atopic as diagnosed using the ADRN Standard Diagnostic Criteria
• are willing to sign the informed consent form or whose parent or legal guardian is willing to sign the informed consent form (age appropriate) prior to initiation of any study procedure
• are willing to sign the assent form, if age appropriate.

You may not qualify if:

• Participants who meet any of the following criteria are not eligible for enrollment:
• have a history of any systemic illness (e.g., immunodeficiency disorders such as human immunodeficiency virus \[HIV\] or lupus erythematosus) other than the condition being studied
• have an active systemic malignancy, excluding uncomplicated non-melanoma skin cancer
• have any skin disease other than AD that might compromise the stratum corneum barrier (e.g., bullous disease, psoriasis, cutaneous T cell lymphoma \[also called Mycosis Fungoides or Sezary syndrome\], dermatitis herpetiformis, Hailey-Hailey, or Darier's disease)
• have a first degree relative already enrolled in the study
• are determined not to be eligible in the opinion of the Investigator.
• Participants who meet any of the following criteria are not eligible for enrollment but may be reassessed:
• have active eczema herpeticum at the Enrollment Visit
• have taken systemic immunosuppressive drugs including cyclosporine or oral steroids within 30 days of the Enrollment Visit
• have a fever ≥ 38.5 degrees Centigrade (ºC) (101.3 ºF) at the Enrollment Visit.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Atopic Dermatitis Research Network: collaborator

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Related Publications (2)

• Gao L, Bin L, Rafaels NM, Huang L, Potee J, Ruczinski I, Beaty TH, Paller AS, Schneider LC, Gallo R, Hanifin JM, Beck LA, Geha RS, Mathias RA, Barnes KC, Leung DYM. Targeted deep sequencing identifies rare loss-of-function variants in IFNGR1 for risk of atopic dermatitis complicated by eczema herpeticum. J Allergy Clin Immunol. 2015 Dec;136(6):1591-1600. doi: 10.1016/j.jaci.2015.06.047. Epub 2015 Sep 3.

  PMID: 26343451 RESULT

• Bin L, Edwards MG, Heiser R, Streib JE, Richers B, Hall CF, Leung DY. Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum. J Allergy Clin Immunol. 2014 Oct;134(4):848-55. doi: 10.1016/j.jaci.2014.07.018. Epub 2014 Aug 23.

  PMID: 25159465 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples, RNA, serum, protein and cells will be retained.

MeSH Terms

Conditions

Dermatitis, Atopic; Kaposi Varicelliform Eruption; Herpes Simplex

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious

Study Officials

• Donald Leung, PhD, M.D

  National Jewish Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2011
• First Posted: September 7, 2011
• Study Start: April 1, 2011
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: April 28, 2017

Record last verified: 2017-04

Locations

US (1)